Orally disintegrating tablets are oral solid preparations that rapidly disintegrate in an oral cavity only in saliva in the oral cavity or a small amount of water in about 30 seconds or less. Since orally disintegrating tablets rapidly disintegrate in an oral cavity, the tablets are preparations that patients can easily take, and in particular, the needs of the elderly and children, who have difficulties in swallowing, for the tablets have been growing.
However, even immediately after produced, many orally disintegrating tablets generally have lower tablet hardness than typical oral solid preparations and are hygroscopic due to the influence of sugars, disintegrants, and other ingredients that are contained in the tablets in order to improve the disintegration property of the tablets. Therefore, many orally disintegrating tablets are difficult to store under high humidity conditions and to package in a single-dose pack.
Furthermore, generally, film coating over an oral solid preparation, such as a tablet and a granule, has been widely applied for the purpose of maintaining hardness and controlling hygroscopicity thereof. The film coating is applied for the purpose of protecting or stabilizing an active ingredient from environmental factors, such as humidity and light. Alternatively, the film coating is also applied for the purpose of giving moisture resistance to a tablet to maintain tablet hardness. Alternatively, the film coating is often applied for the purpose of masking the bitterness and odor of a pharmaceutical drug. Furthermore, in the case where an active ingredient is a hyperactive ingredient, such as an anticancer agent or an agent acting on hormone, it should be avoided that not only a distribution process, but also health care professionals on the front lines of health care are exposed to the hyperactive ingredient, and it is undesirable to unnecessarily expose a patient himself/herself to the hyperactive ingredient. Also in terms of safety measures against such exposure, the film coating is considered to be useful. Together with a proper amount of water, a patient takes such conventional film-coated oral solid preparation in the as-is status. That is, a conventional film-coated oral solid preparation is taken by a patient in a state in which a film coating layer of the preparation is not completely dissolved in the oral cavity of the patient.
As described above, many orally disintegrating tablets generally have lower tablet hardness than typical oral solid preparations and are hygroscopic, and therefore, the foregoing film coating technique is expected to be applied to orally disintegrating tablets, and actually, such application have gone through some trials. However, in the application of this film coating technique to orally disintegrating tablets, there are problems specific to orally disintegrating tablets. An orally disintegrating tablet coated with film needs to be such that a film coating layer thereof rapidly dissolves in the oral cavity of a patient, and subsequently, a body of the tablet also rapidly disintegrates. Furthermore, naturally, in the dissolution of the film coating layer of an orally disintegrating tablet coated with film in the oral cavity of a patient, the taste and mouth-feel also need to be considered.
Furthermore, orally disintegrating tablets have the property of rapidly dissolving with a small amount of water, and therefore, an orally disintegrating tablet coated with film needs a measure, for example, to prevent the tablet from disintegrating during a film coating process, and hence, the application of film coating to an orally disintegrating tablet is extremely difficult.
Japanese Patent Application Laid-Open No. 2001-192344 provides an oral solid preparation that is coated with a film coating agent wherein the blending weight ratio of methylcellulose to an acrylic polymer is from 5:95 to 60:40. Furthermore, Japanese Patent Application Laid-Open No. 2001-192344 describes a technique of coating granulation particles with said film coating agent, and then molding an uncoated orally disintegrating tablet. However, Japanese Patent Application Laid-Open No. 2001-192344 does not disclose a technique of applying film-coating to an orally disintegrating tablet itself. Furthermore, according to the description of Examples of Japanese Patent Application Laid-Open No. 2001-192344, in the particles of Examples coated by the foregoing technique, the time elapsed before bitterness was felt, that is, the time elapsed before a film coating layer dissolved was 30 seconds or more. Hence, in the case where the entire surface of an uncoated orally disintegrating tablet is film-coated with the film coating agent described in Examples of Japanese Patent Application Laid-Open No. 2001-192344, it is hard to expect that the film coating layer in the surface of the orally disintegrating tablet rapidly dissolves. Therefore, even if the film coating agent described in Japanese Patent Application Laid-Open No. 2001-192344 is applied to an orally disintegrating tablet, it is thought to be difficult to result in obtaining an orally disintegrating tablet coated with film having a rapid disintegration property.
Japanese Patent Application Laid-Open No. 2008-280316 describes that a dry-coated orally disintegrating tablet comprising an inner core and a coated layer is coated with a coating agent produced by adding Macrogol 6000 and titanium oxide to a cellulose derivative, such as hydroxymethyl propyl cellulose, hydroxymethyl cellulose, or methylcellulose.
Japanese Patent Application Laid-Open No. 2013-155148 describes a technique of film-coating an orally disintegrating tablet with a coating liquid in which a compound selected from polyvinyl-alcohol polymers and a discoloration-inducing metal oxide are dispersed in order to UV-laser-print characters and the like on the surface of the orally disintegrating tablet for the purpose of improving distinguishability.
However, according to the specification of Japanese Patent Application Laid-Open No. 2008-280316, the inventors of Japanese Patent Application Laid-Open No. 2008-280316 thought that common orally disintegrating tablets primarily have no sufficient hardness, and hence, film coating cannot be applied to such tablets, and therefore, the inventors produced a new preparation, that is, a dry-coated tablet capable of dissolving in an oral cavity. Furthermore, the technique described in Japanese Patent Application Laid-Open No. 2008-280316 is to coat the dry-coated tablet capable of dissolving in an oral cavity with the foregoing coating agent, and therefore, this technique cannot be applied to common orally disintegrating tablets. As for orally disintegrating tablets of Examples described in Japanese Patent Application Laid-Open No. 2013-155148, the time elapsed before an uncoated orally disintegrating tablet disintegrated in an oral cavity was approximately 30 seconds, in contrast, the time elapsed before a coated orally disintegrating tablet disintegrated in an oral cavity was approximately 60 seconds. Thus, a coating liquid described in Japanese Patent Application Laid-Open No. 2013-155148 has a practical problem because another 30 seconds is required for the oral disintegration due to the film coating.
WO 2010/113841 describes a stable coated orally disintegrating tablet containing a drug other than nalfurafine or a pharmaceutically acceptable salt thereof, wherein the tablet is coated with a coating layer containing a water-soluble substance and a polyvinyl alcohol resin, the coating layer having the weight ratio of the polyvinyl alcohol resin to the water-soluble substance of from 1:0.1 to 1:9, the water-soluble substance being at least one of maltose, maltitol, sorbitol, xylitol, fructose, glucose, lactitol, isomaltose, lactose, erythritol, mannitol, trehalose, and sucrose, dissolving in an amount of 1 g or more in less than 10 mL of water at 20° C., having a hydroxyl group in its molecule, and having a molecular weight of not more than 200 per unit hydroxyl group.
Japanese Patent Application Laid-Open No. 2010-248106 describes an orally disintegrating tablet coated with film comprising a film coating layer, the layer containing: at least one water-soluble polymer selected from the group consisting of hypromellose, hydroxypropylcellulose, water-soluble vinyl derivatives, and starches; and at least one plasticizer selected from the group consisting of polyethylene glycol, polysorbate, propylene glycol, triacetin, and triethyl citrate.
However, in WO 2010/113841 and Japanese Patent Application Laid-Open No. 2010-248106, although the dissolution time and plasticity of the film coating layer are considered, the feel of an orally disintegrating tablet when the tablet is taken, such as taste or mouth-feel, which is the most important for the tablet, and ease of production are not examined in detail.
After a patent application on which the present invention is based, WO 2014/157264 discloses an orally disintegrating tablet coated with film that contains at least one sweetener and is film-coated with at least one cellulose resin selected from methylcellulose, hypromellose, hydroxypropylcellulose, and hypromellose acetate succinate.